NAPOLI-3
In metastatic pancreatic ductal adenocarcinoma, does NALIRIFOX improve survival over gemcitabine plus nab-paclitaxel?
One underlying study; aliases and follow-up reports consolidated. Primary discipline: Medical.
770 patients with previously untreated metastatic pancreatic ductal adenocarcinoma.
Metastatic PDAC suitable for combination chemotherapy; fitness and organ function affect applicability.
770 (383 vs 387) randomised/evaluable as reported.
NALIRIFOX q2w: liposomal irinotecan 50 mg/m², oxaliplatin 60 mg/m², leucovorin 400 mg/m² and infusional 5-FU 2,400 mg/m².
Gemcitabine 1,000 mg/m² plus nab-paclitaxel 125 mg/m² days 1, 8, 15 every 28 days.
Endpoints and results
Primary OS; PFS, response and safety secondary.
- Median OS 11.1 vs 9.2 months; HR 0.83 (95% CI 0.70–0.99; p=0.036).
- Median PFS 7.4 vs 5.6 months; HR 0.69 (95% CI 0.58–0.83; p<0.001).
- 12-month OS 45.6% vs 39.5%. Grade ≥3 treatment-emergent AEs ~87% vs 86%; treatment-related deaths ~2% each.
Absolute Effect and outcome visualisation
12-month OS
% alive at 12 months · 12 months. Bars show source-reported fixed-time percentages.
Interpretation: 6.1-point 12-month OS difference; approximate landmark NNT 17 at 12 months, calculated from fixed-time rates.
Toxicity, discontinuation and quality of life
Trial-specific harms: Grade ≥3 AEs common in both arms; NALIRIFOX diarrhoea, nausea, neutropenia and neuropathy; comparator also causes cytopenias and neuropathy.
Treatment burden/discontinuation: Both are intensive regimens; compare infusion schedule, dose modifications, access and patient preference.
Quality of life: No numeric comparative QoL estimate asserted here.
Subgroups, maturity and limitations
Subgroups: No unverified subgroup-specific survival claim; assess performance status and fitness.
Maturity: Phase III primary report published 2023.
Limitations: High toxicity burden in both arms; median OS gain is modest although fixed-time OS differs.
NAPOLI-3 supports NALIRIFOX as a first-line option for fit patients with metastatic PDAC, with a six-point 12-month OS gain and substantial toxicity.
Use current regional guidelines, patient fitness, biomarkers, competing risks, alternatives and regulatory status before clinical application. Clinical freshness review and browser-rendered QA remain pending.
Primary sources and registry
Registry: NCT04083235
The Absolute Effect · Updated 26 October 2026 · Never derive NNT from median survival.